Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice
Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of TH-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity to 3-mercaptopropionic acid and differential enhancement of TH-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of TH-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.
- Research Organization:
- Univ. of Colorado, Boulder
- OSTI ID:
- 6360374
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 40:23; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CORRELATIONS
DATA
DISEASES
DRUGS
EXPERIMENTAL DATA
HYPNOTICS AND SEDATIVES
INFORMATION
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MICE
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES